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The NMDA receptor functions independently and as an LRP1 co-receptor to promote Schwann cell surv...http://biblioteca.universia.net/html_bura/ficha/params/title/the-nmda-receptor-functions-independently-and-as-an-lrp1-co/id/67621284.html
NMDA receptors (NMDA-Rs) are ionotropic glutamate receptors, which associate with LDL-receptor-related protein-1 (LRP1) to trigger cell signaling in response to protein ligands in neurons. Here, we demonstrate for the first time that the NMDA-R is expressed by rat Schwann cells and functions independently and with LRP1 to regulate Schwann cell physiology. The NR1 (encoded by GRIN1) and NR2b (encoded by GRIN2B) NMDA-R subunits were expressed by cultured Schwann cells and upregulated in sciatic...Mantuano, Elisabetta; Lam, Michael S.; Shibayama, Masataka; Campana, W. Marie; Gonias, Steven L.Vinculin phosphorylation at residues Y100 and Y1065 is required for cellular force transmissionhttp://biblioteca.universia.net/html_bura/ficha/params/title/vinculin-phosphorylation-at-residues-y100-and-y1065-is-required-for/id/67621252.html
The focal adhesion protein vinculin connects the actin cytoskeleton, through talin and integrins, with the extracellular matrix. Vinculin consists of a globular head and tail domain, which undergo conformational changes from a closed auto-inhibited conformation in the cytoplasm to an open conformation in focal adhesions. Src-mediated phosphorylation has been suggested to regulate this conformational switch. To explore the role of phosphorylation in vinculin activation, we used knock-out mouse...Auernheimer, Vera; Lautscham, Lena A.; Leidenberger, Maria; Friedrich, Oliver; Kappes, Barbara; Fabry, Ben; Goldmann, Wolfgang H.Induction of lateral lumens through disruption of a monoleucine-based basolateral-sorting motif i...http://biblioteca.universia.net/html_bura/ficha/params/title/induction-of-lateral-lumens-through-disruption-of-monoleucine-based-basolateral/id/67621251.html
Directed delivery of EGF receptor (EGFR) ligands to the apical or basolateral surface is a crucial regulatory step in the initiation of EGFR signaling in polarized epithelial cells. Herein, we show that the EGFR ligand betacellulin (BTC) is preferentially sorted to the basolateral surface of polarized MDCK cells. By using sequential truncations and site-directed mutagenesis within the BTC cytoplasmic domain, combined with selective cell-surface biotinylation and immunofluorescence, we have un...Singh, Bhuminder; Bogatcheva, Galina; Starchenko, Alina; Sinnaeve, Justine; Lapierre, Lynne A.; Williams, Janice A.; Goldenring, James R.; Coffey, Robert J.Volume regulation and shape bifurcation in the cell nucleushttp://biblioteca.universia.net/html_bura/ficha/params/title/volume-regulation-and-shape-bifurcation-in-the-cell-nucleus/id/67621250.html
Alterations in nuclear morphology are closely associated with essential cell functions, such as cell motility and polarization, and correlate with a wide range of human diseases, including cancer, muscular dystrophy, dilated cardiomyopathy and progeria. However, the mechanics and forces that shape the nucleus are not well understood. Here, we demonstrate that when an adherent cell is detached from its substratum, the nucleus undergoes a large volumetric reduction accompanied by a morphologica...Kim, Dong-Hwee; Li, Bo; Si, Fangwei; Phillip, Jude M.; Wirtz, Denis; Sun, Sean X.Centrosomal AKAP350 and CIP4 act in concert to define the polarized localization of the centrosom...http://biblioteca.universia.net/html_bura/ficha/params/title/centrosomal-akap350-and-cip4-act-in-concert-to-define-the/id/67011993.html
The acquisition of a migratory phenotype is central in processes as diverse as embryo differentiation and tumor metastasis. An early event in this phenomenon is the generation of a nucleus–centrosome–Golgi back-to-front axis. AKAP350 (also known as AKAP9) is a Golgi and centrosome scaffold protein that is involved in microtubule nucleation. AKAP350 interacts with CIP4 (also known as TRIP10), a cdc42 effector that regulates actin dynamics. The present study aimed to characterize the participat...Tonucci, Facundo M.; Hidalgo, Florencia; Ferretti, Anabela; Almada, Evangelina; Favre, Cristián; Goldenring, James R.; Kaverina, Irina; Kierbel, Arlinet; Larocca, M. CeciliaCooperative interactions of LPPR family members in membrane localization and alteration of cellul...http://biblioteca.universia.net/html_bura/ficha/params/title/cooperative-interactions-of-lppr-family-members-in-membrane-localization-and/id/67011992.html
The lipid phosphate phosphatase-related proteins (LPPRs), also known as plasticity-related genes (PRGs), are classified as a new brain-enriched subclass of the lipid phosphate phosphatase (LPP) superfamily. They induce membrane protrusions, neurite outgrowth or dendritic spine formation in cell lines and primary neurons. However, the exact roles of LPPRs and the mechanisms underlying their effects are not certain. Here, we present the results of a large-scale proteome analysis to determine LP...Yu, Panpan; Agbaegbu, Chinyere; Malide, Daniela A.; Wu, Xufeng; Katagiri, Yasuhiro; Hammer, John A.; Geller, Herbert M.The miR-199–dynamin regulatory axis controls receptor-mediated endocytosishttp://biblioteca.universia.net/html_bura/ficha/params/title/the-mir-199–dynamin-regulatory-axis-controls-receptor-mediated-endocytosis/id/67011991.html
Small non-coding RNAs (microRNAs) are important regulators of gene expression that modulate many physiological processes; however, their role in regulating intracellular transport remains largely unknown. Intriguingly, we found that the dynamin (DNM) genes, a GTPase family of proteins responsible for endocytosis in eukaryotic cells, encode the conserved miR-199a and miR-199b family of miRNAs within their intronic sequences. Here, we demonstrate that miR-199a and miR-199b regulate endocytic tr...Aranda, Juan F.; Canfrán-Duque, Alberto; Goedeke, Leigh; Suárez, Yajaira; Fernández-Hernando, CarlosEpigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-ind...http://biblioteca.universia.net/html_bura/ficha/params/title/epigenetic-modifiers-reduce-inflammation-and-modulate-macrophage-phenotype-during-endotoxemia/id/66121434.html
Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema and respiratory failure. Here, we examined the efficacy the DNA methyl transferase (DNMT) inhibitor 5-Aza 2-deoxycytidine (Aza), the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), as well as the combination therapy of Aza and TSA (Aza+TSA) provides in the protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed substantial attenuation of adve...Thangavel, Jayakumar; Samanta, Saheli; Rajasingh, Sheeja; Barani, Bahar; Xuan, Yu-Ting; Dawn, Buddhadeb; Rajasingh, JohnsonEndothelial MMP14 is required for endothelial-dependent growth support of human airway basal cellshttp://biblioteca.universia.net/html_bura/ficha/params/title/endothelial-mmp14-is-required-for-endothelial-dependent-growth-support-of/id/66121433.html
Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated sig...Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.Robust hematopoietic progenitor cell commitment in the presence of a conflicting cuehttp://biblioteca.universia.net/html_bura/ficha/params/title/robust-hematopoietic-progenitor-cell-commitment-in-the-presence-of-conflicting/id/66121432.html
Hematopoietic lineage commitment is regulated by cytokines and master transcription factors, but it remains unclear how a progenitor cell chooses a lineage in the face of conflicting cues. Through transcript counting in megakaryocyte–erythroid progenitors undergoing erythropoiesis, we show that the expression levels of the pro-erythropoiesis transcription factor EKLF (also known as KLF1) and receptor EpoR are inversely correlated with their pro-megakaryopoiesis counterparts, FLI-1 and TpoR (a...Shah, Najaf A.; Levesque, Marshall J.; Raj, Arjun; Sarkar, Casim A.The Exocyst at a Glancehttp://biblioteca.universia.net/html_bura/ficha/params/title/the-exocyst-at-glance/id/66121431.html
The exocyst is an octameric protein complex that is implicated in the tethering of secretory vesicles to the plasma membrane prior to SNARE-mediated fusion. Spatial and temporal control of exocytosis through the exocyst has a crucial role in a number of physiological processes, such as morphogenesis, cell cycle progression, primary ciliogenesis, cell migration and tumor invasion. In this Cell Science at a Glance poster article, we summarize recent works on the molecular organization, function...Wu, Bin; Guo, WeiIdentification of RNF168 as a PML nuclear body regulatorhttp://biblioteca.universia.net/html_bura/ficha/params/title/identification-of-rnf168-as-pml-nuclear-body-regulator/id/65955040.html
Promyelocytic leukemia (PML) protein forms the basis of PML nuclear bodies (PML NBs), which control many important processes. We have screened an shRNA library targeting ubiquitin pathway proteins for effects on PML NBs, and identified RNF8 and RNF168 DNA-damage response proteins as negative regulators of PML NBs. Additional studies confirmed that depletion of either RNF8 or RNF168 increased the levels of PML NBs and proteins, whereas overexpression induced loss of PML NBs. RNF168 partially l...Shire, Kathy; Wong, Andrew I.; Tatham, Michael H.; Anderson, Oliver F.; Ripsman, David; Gulstene, Stephanie; Moffat, Jason; Hay, Ronald T.; Frappier, LoriMitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis wit...http://biblioteca.universia.net/html_bura/ficha/params/title/mitf-is-master-regulator-of-the-v-atpase-forming-control/id/65953598.html
The v-ATPase is a fundamental eukaryotic enzyme that is central to cellular homeostasis. Although its impact on key metabolic regulators such as TORC1 is well documented, our knowledge of mechanisms that regulate v-ATPase activity is limited. Here, we report that the Drosophila transcription factor Mitf is a master regulator of this holoenzyme. Mitf directly controls transcription of all 15 v-ATPase components through M-box cis-sites and this coordinated regulation affects holoenzyme activity...Zhang, Tianyi; Zhou, Qingxiang; Ogmundsdottir, Margret Helga; Möller, Katrin; Siddaway, Robert; Larue, Lionel; Hsing, Michael; Kong, Sek Won; Goding, Colin Ronald; Palsson, Arnar; Steingrimsson, Eirikur; Pignoni, FrancescaAnalysis of ER–mitochondria contacts using correlative fluorescence microscopy and soft X-ray tom...http://biblioteca.universia.net/html_bura/ficha/params/title/analysis-of-er–mitochondria-contacts-using-correlative-fluorescence-microscopy-and-soft/id/65953597.html
Mitochondrial fission is important for organelle transport, quality control and apoptosis. Changes to the fission process can result in a wide variety of neurological diseases. In mammals, mitochondrial fission is executed by the GTPase dynamin-related protein 1 (Drp1; encoded by DNM1L), which oligomerizes around mitochondria and constricts the organelle. The mitochondrial outer membrane proteins Mff, MiD49 (encoded by MIEF2) and MiD51 (encoded by MIEF1) are involved in mitochondrial fission ...Elgass, Kirstin D.; Smith, Elizabeth A.; LeGros, Mark A.; Larabell, Carolyn A.; Ryan, Michael T.Access of torsinA to the inner nuclear membrane is activity dependent and regulated in the endopl...http://biblioteca.universia.net/html_bura/ficha/params/title/access-of-torsina-to-the-inner-nuclear-membrane-is-activity/id/65953596.html
TorsinA (also known as torsin-1A) is a membrane-embedded AAA+ ATPase that has an important role in the nuclear envelope lumen. However, most torsinA is localized in the peripheral endoplasmic reticulum (ER) lumen where it has a slow mobility that is incompatible with free equilibration between ER subdomains. We now find that nuclear-envelope-localized torsinA is present on the inner nuclear membrane (INM) and ask how torsinA reaches this subdomain. The ER system contains two transmembrane pro...Goodchild, Rose E.; Buchwalter, Abigail L.; Naismith, Teresa V.; Holbrook, Kristen; Billion, Karolien; Dauer, William T.; Liang, Chun-Chi; Dear, Mary Lynn; Hanson, Phyllis I.Akt signaling dynamics in individual cellshttp://biblioteca.universia.net/html_bura/ficha/params/title/akt-signaling-dynamics-in-individual-cells/id/65911144.html
The protein kinase Akt (for which there are three isoforms) is a key intracellular mediator of many biological processes, yet knowledge of Akt signaling dynamics is limited. Here, we have constructed a fluorescent reporter molecule in a lentiviral delivery system to assess Akt kinase activity at the single cell level. The reporter, a fusion between a modified FoxO1 transcription factor and clover, a green fluorescent protein, rapidly translocates from the nucleus to the cytoplasm in response ...Gross, Sean M.; Rotwein, PeterActivated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell dea...http://biblioteca.universia.net/html_bura/ficha/params/title/activated-microglia-cause-reversible-apoptosis-of-pheochromocytoma-cells-inducing-their/id/65879808.html
Some apoptotic processes, such as phosphatidylserine exposure, are potentially reversible and do not necessarily lead to cell death. However, phosphatidylserine exposure can induce phagocytosis of a cell, resulting in cell death by phagocytosis: phagoptosis. Phagoptosis of neurons by microglia might contribute to neuropathology, whereas phagoptosis of tumour cells by macrophages might limit cancer. Here, we examined the mechanisms by which BV-2 microglia killed co-cultured pheochromocytoma (P...Hornik, Tamara C.; Vilalta, Anna; Brown, Guy C.Assembly and maintenance of the flagellum attachment zone filament in Trypanosoma bruceihttp://biblioteca.universia.net/html_bura/ficha/params/title/assembly-and-maintenance-of-the-flagellum-attachment-zone-filament-in/id/65878447.html
Adhesion of motile flagella to the cell body in Trypanosoma brucei requires a filamentous cytoskeletal structure termed the flagellum attachment zone (FAZ). Despite its essentiality, the complete molecular composition of the FAZ filament and its roles in FAZ filament assembly remain poorly understood. By localization-based screening, we here identified a new FAZ protein, which we called FAZ2. Knockdown of FAZ2 disrupted the FAZ filament, destabilized multiple FAZ filament proteins and caused ...Zhou, Qing; Hu, Huiqing; He, Cynthia Y.; Li, ZiyinCALHM1 ion channel elicits amyloid-β clearance by insulin-degrading enzyme in cell lines and in v...http://biblioteca.universia.net/html_bura/ficha/params/title/calhm1-ion-channel-elicits-amyloid-β-clearance-by-insulin-degrading/id/65878446.html
Alzheimer's disease is characterized by amyloid-β (Aβ) peptide accumulation in the brain. CALHM1, a cell-surface Ca2+ channel expressed in brain neurons, has anti-amyloidogenic properties in cell cultures. Here, we show that CALHM1 controls Aβ levels in vivo in the mouse brain through a previously unrecognized mechanism of regulation of Aβ clearance. Using pharmacological and genetic approaches in cell lines, we found that CALHM1 ion permeability and extracellular Ca2+ were required for the A...Vingtdeux, Valérie; Chandakkar, Pallavi; Zhao, Haitian; Blanc, Lionel; Ruiz, Santiago; Marambaud, PhilippeDiffering roles of pyruvate dehydrogenase kinases during mouse oocyte maturationhttp://biblioteca.universia.net/html_bura/ficha/params/title/differing-roles-of-pyruvate-dehydrogenase-kinases-during-mouse-oocyte-maturation/id/65878242.html
Pyruvate dehydrogenase kinases (PDKs) modulate energy homeostasis in multiple tissues and cell types, under various nutrient conditions, through phosphorylation of the α subunit (PDHE1α, also known as PDHA1) of the pyruvate dehydrogenase (PDH) complex. However, the roles of PDKs in meiotic maturation are currently unknown. Here, by undertaking knockdown and overexpression analysis of PDK paralogs (PDK1–PDK4) in mouse oocytes, we established the site-specificity of PDKs towards the phosphoryla...Hou, Xiaojing; Zhang, Liang; Han, Longsen; Ge, Juan; Ma, Rujun; Zhang, Xuesen; Moley, Kelle; Schedl, Tim; Wang, Qiang